Jamel Zaouali

Cerebral Venous Thrombosis: Clinical Features, Risk Factors, and Long-term Outcome in a Tunisian Cohort

BACKGROUND Data from African countries regarding diagnosis, prognosis, management, and outcome of patients with cerebral venous thrombosis (CVT) are limited. The aim of the present study is to characterize clinical presentation, predisposing factors, neuroimaging findings, and outcomes of the disease in the Tunisian population. METHODS This is a prospective study including patients referred to the Neurology Department of the Military Hospital of Tunis between January 2009 and December 2012. The diagnosis of CVT was confirmed in all patients using magnetic resonance imaging and magnetic resonance venography. The demographic, clinical, radiological, and outcome data were recorded and analyzed. Median follow-up was 16 months (range 6 months to 4 years). Primary outcome was death or dependency as assessed by modified Rankin score more than 2 at the end of follow-up. RESULTS This study included 41 patients with CVT. Mean age was 41.24 years, predominantly women (68%). The mode of onset was acute in 10 patients (24%), subacute in 26 (64%), and chronic in 5 (12%). The most common presenting features were headache, observed in 83% of the patients, followed by seizures, focal motor deficits, papilledema, and mental status changes. Lateral (56%) and superior longitudinal (51%) sinuses were the most commonly involved. Multiple sinuses were involved in 46% of cases. Nineteen patients (46%) had a D-dimer level more than 500 ng/mL. Major causes of CVT were thrombophilia (56%), either genetic or acquired, obstetric and gynecological (50%), and septic (34%). Outcome was favorable in 83% of patients. At the end of follow-up, 32 patients (78%) had complete recovery (modified Rankin Scale [mRs] score 0-1), 2 (5%) had partial recovery (mRs score 2), and 4 (10%) were dependent (mRs score 3-5). One patient (2.5%) had a recurrent sinus thrombosis. CONCLUSIONS Our Tunisian population presented distinct risk factors profile with high frequency of thrombophilia, infections, and postpartum state. Oral contraceptive use is not a major risk factor in our population. The overall prognosis was good.

Association of HLA-DR/DQ polymorphisms with Guillain–Barré syndrome in Tunisian patients

UNLABELLED Human leukocyte antigen (HLA) alleles have been implicated in many autoimmune diseases. The aim of this study is to assess whether HLA-DR/DQ alleles confer susceptibility to Guillain-Barré syndrome (GBS) in a Tunisian population. METHODS The HLA-DR/DQ genotyping was performed using polymerase chain reaction sequence-specific primers (PCR-SSP) in 38 patients with GBS and 100 healthy Tunisian control subjects. RESULTS GBS in Tunisian patients was found to be associated with the following alleles with these relative patient versus control frequencies (pc denotes Bonferroni corrected probability values): DRB1*13 (23.68% vs. 9.0%; pc=0.01), followed by DRB1*14 (22.36% vs.5.5%; pc<10(-3)). Two haplotypes, DRB1*14/DQB1*05 and DRB1*13/DQB1*03, were found to be associated with susceptibility to GBS. However DRB1*07/DQB1*02 and DRB1*03/DQB1*02 haplotypes were more frequently observed in controls than in patients (11.5% vs.7.9%; pc=0.007 and 23% vs. 5.26%; pc<10(-3) respectively). These haplotypes seem to confer protection against the disease. CONCLUSION Our data demonstrated a new GBS predisposition associated with HLA-DRB1*14 and DRB1*13. Theses alleles could be predisposing genetic factors for GBS in the Tunisian population.

Association of HLA-DR/DQ polymorphism with myasthenia gravis in Tunisian patients.

BACKGROUND AND OBJECTIVE Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction. MG has been shown to be associated with many human leukocyte antigens (HLA) in different populations. The aim of this study was to investigate the probable association between HLA-DR/DQ alleles and MG in Tunisian patients. PATIENTS AND METHODS HLA DR/DQ genotyping was performed using polymerase chain reaction sequence-specific primers (PCR-SSP) with 48 MG patients and 100 healthy individuals serving as the control group. RESULTS Myasthenia gravis in Tunisian patients was found to be associated with the following alleles (p(c) denotes Bonferroni corrected probability values): HLA-DRB1*03 (p(c)<10(-3)), DRB1*04 (p(c)=0.005), DQB1*02 (p(c)=0.002) and, DQB1*03 (p(c)=0.007). CONCLUSION Our data demonstrated a new HLA-MG predisposition with DRB1*04. The DRB1*03, DRB1*04, DQB1*02, and DQB1*03 alleles also could be predisposing genetic factors for MG in the Tunisian population.

Association of methylenetetrahydrofolate reductase A1298C polymorphism but not of C677T with multiple sclerosis in Tunisian patients

BACKGROUND AND OBJECTIVE Multiple sclerosis (MS) is a chronic neurological disease characterized by central nervous system (CNS) inflammation and demyelination of nerve axons. The aim of this study was to investigate a possible association between the methylenetetrahydrofolate reductase (MTHFR) gene and multiple sclerosis in Tunisian patients. PATIENTS AND METHODS The genotyping of two missense variants of the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C was performed in 80 multiple sclerosis patients and 200 healthy controls. RESULTS No significant differences were found in the frequency of the MTHFR C677T polymorphism between MS patients and healthy controls. However, the genotype prevalence of the missense variant MTHFR A1298C was significantly different between patients and controls (A/C: 55% versus 7%, p<10(-3); C/C: 13.75% versus 0%, p<10(-3), respectively). CONCLUSION Although our preliminary findings suggest no association between the MTHFR C677T variants and MS, there is evidence to suggest a significant association between the MTHFR A1298C polymorphisms and MS.

Apolipoprotein E Genotypes Associated with Alzheimer Disease and Concomitant Stroke

BACKGROUND The ɛ4 allele of the apolipoprotein E (APOE) gene is a well-characterized genetic risk factor for Alzheimer disease (AD). The association between stroke and a higher risk for AD has also been reported. Our study sought to determine the relationship between the APOE gene and AD and the comorbid risk of stroke. METHODS The subjects of this study consisted of 48 patients with AD and 48 members of a control group. All subjects were genotyped for APOE. RESULTS The results clearly show a significant increased risk of AD in carriers of the APOE ε3/ε4 genotype (P = .003, odds ratio [OR] = 4.1) or ε4 allele (P = .001, OR = 4.2). The risk for stroke in AD patients was also increased for carriers of the APOE ε3/ε4 genotype (P = .02, OR = 9.0) and for carriers of the APOE ε4 allele (P = .004, OR = 5.5). CONCLUSIONS The present study is the first to establish a relationship between APOE ε4 and concomitant AD and stroke in the Tunisian population.

Limbic encephalitis associated with leucine-rich glioma-inactivated 1 antibodies.

We describe the case of a patient with confirmed limbic encephalitis associated with leucine-rich glioma-inactivated 1 (LGI1) antibodies. A 59-year-old man presented to the Department of Neurology with bizarre behavior, memory loss, cognitive impairment, visual hallucinations, and myoclonus and faciobrachial dystonic seizures. A brain magnetic resonance imaging (MRI) revealed no hippocampal lesions. Blood tests showed hyponatremia. An electroencephalogram showed disorganization and slowing of background activity. Antiepileptic drugs were ineffective. The patient exhibited considerable improvement following immunotherapy. The diagnosis of limbic encephalitis associated with LGI1 antibodies should be considered in patients with clinical manifestations mimicking psychiatric disorders and in cases of refractory epilepsy especially with faciobrachial dystonic seizures. There is frequently hyponatremia, and cerebral MRI may be normal. Full recovery can be expected with early diagnosis and prompt treatment.

Transient global amnesia like syndrome associated with acute infarction of the corpus callosum: a case report

The corpus callosum (CC) constitutes the largest white matter bundle and it connects the two cerebral hemispheres [1]. Infarction of the CC is rare. The clinical picture varies from an acute onset to slow evolving symptoms, frequently with poor localizing signs; however, the location of the infarct in the callosum often correlates with a specific etiology [2]. In previous studies, lesions in the CC caused permanent, but not transient global amnesia (TGA) by involving the thalamocortical portion of the Papez’ circuit. We present a patient with TGA like syndrome after a corpus callosum infarct to highlight its involvement in cognitive impairments. We discuss the pathophysiology of this rare entity and the more important clinical symptomatologies.

Role of methylenetetrahydrofolate reductase A1298C polymorphism in cerebral venous thrombosis.

The association between the methylenetetrahydrofolate reductase (MTHFR) gene and cerebral venous thrombosis (CVT) remains controversial. This study principally investigated the potential role of the MTHFR A1298C variant and CVT. The genotyping of the A1298C variant of the MTHFR gene was performed in 35 CVT patients and 200 healthy controls. The frequency of A1298C genotype among CVT patients was significantly higher compared with controls (P < 10−3), suggesting an association between this polymorphism and CVT. To our knowledge, there are no previous reports assessing the correlation between the MTHFR A1298C variant and CVT. Large study populations would be required to understand the contribution of this marker in the risk of CVT.

Cognitive impairment in celiac disease and non-celiac gluten sensitivity: review of literature on the main cognitive impairments, the imaging and the effect of gluten free diet

Celiac disease (CD) and non celiac gluten sensitivity (NCGS) can be responsible for neurological complications such as ataxia and peripheral neuropathies but also cognitive impairment. This cognitive involvement is variable in its expression, its duration and its prognosis ranging from transient and reversible subtle involvement to dementia itself. Through this article, we tried to achieve a review of the literature to better understand this topic. Several mechanisms were proposed to explain the deleterious influence of gluten-related pathologies on cognitive functions: nutritional deficiencies, elevation of circulating cytokine levels due to systemic inflammation, low brain serotonin levels… Several types of dementia such as Alzheimer dementia, vascular dementia, frontotemporal dementia were reported in association with CD. Memory disorder, acalculia, inattention, visuospatial deficits and executive dysfunction must be sought systematically by a neuropsychological assessment in patients with CD or NCGS. As far as the cognitive impairment is concerned, there is no pathognomonic radiological lesion. Concerning therapeutic management; although its effect is controversial, gluten free diet should be introduced, as early as possible, because of its potentially protective effect.

Occipital Sinus Thrombosis: An Exceptional Case Report

BACKGROUND Variations of the dural venous sinuses may result in inaccurate imaging interpretation or complications during surgical approaches. One variation of the dural venous sinuses reported infrequently in the literature is the occipital sinus. We report an exceptional case of occipital sinus thrombosis. CASE REPORT A 48-year-old right-handed man with a 5-month history of hypertension and chronic renal failure presented with cephalalgia, vomiting, and blurred vision evolving over 48 hours. Neurological examination revealed papillary edema stage 1 with no others abnormalities. An initial brain computed tomography (CT) scan performed was normal. The opening pressure of cerebrospinal fluid (CSF) was 35 cmH2O with normal level of protein and no hypercellularity in CSF analysis. The evolution was marked by the occurrence of generalized tonic-clonic seizure. A second CT scan performed showed a hyperdensity of the occipital sinus. Magnetic resonance imaging and magnetic resonance venography studies confirmed the diagnosis with highlighting the thrombosis of the occipital sinus in association to an ectasia of the torcular. The patient received adequate anticoagulation for 6 months in association to antiepileptic drugs with a good evolution. DISCUSSION According to our review, such a thrombosis must be a rare condition, because our literature search has shown a lack of any report describing this condition. Herein, we review the anatomy of the occipital sinus and we illustrate the characteristics of this unusual thrombosis with multiple imaging modalities. CONCLUSION Understanding of the cerebral venous anatomy and recognition of venous variations essentially help when dealing with a pathology, which presents along with a particular venous variation, no matter how rare this combination is.